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Questions and Answers
What is the primary function of thrombomodulin on endothelial cells?
What is the primary function of thrombomodulin on endothelial cells?
Which of the following is a potential consequence of thrombosis?
Which of the following is a potential consequence of thrombosis?
What primarily causes pulmonary emboli?
What primarily causes pulmonary emboli?
What is the role of the immune system?
What is the role of the immune system?
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Which component is part of the innate immune system?
Which component is part of the innate immune system?
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Which type of embolism is characterized by the presence of abnormal proteins in tissues?
Which type of embolism is characterized by the presence of abnormal proteins in tissues?
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Which best describes adaptive immunity?
Which best describes adaptive immunity?
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What type of cells are responsible for recognizing microbes and damaged cells in the innate immune system?
What type of cells are responsible for recognizing microbes and damaged cells in the innate immune system?
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What is the primary cause of X-SCID?
What is the primary cause of X-SCID?
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Which disease is specifically characterized by a failure of B cell maturation?
Which disease is specifically characterized by a failure of B cell maturation?
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What is a common characteristic of immune deficiency diseases?
What is a common characteristic of immune deficiency diseases?
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Which syndrome is associated with failure of thymus development?
Which syndrome is associated with failure of thymus development?
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Which of the following diseases results from a mutation in the BTK gene?
Which of the following diseases results from a mutation in the BTK gene?
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What role do CD4 and coreceptors play in viral entry into cells?
What role do CD4 and coreceptors play in viral entry into cells?
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How do HIV infections primarily affect the immune system?
How do HIV infections primarily affect the immune system?
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What is a characteristic of common variable immunodeficiency?
What is a characteristic of common variable immunodeficiency?
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What is the primary cause of congenital adrenal hyperplasia (CAH)?
What is the primary cause of congenital adrenal hyperplasia (CAH)?
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Which condition is characterized by systemic infections leading to adrenal failure?
Which condition is characterized by systemic infections leading to adrenal failure?
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What is a common symptom of chronic adrenal insufficiency?
What is a common symptom of chronic adrenal insufficiency?
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Which of the following is a known cause of chronic adrenal insufficiency?
Which of the following is a known cause of chronic adrenal insufficiency?
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Which type of diabetes is primarily caused by destruction of islet beta cells?
Which type of diabetes is primarily caused by destruction of islet beta cells?
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What is the primary target of the HIV virus in the immune system?
What is the primary target of the HIV virus in the immune system?
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What is the purpose of antiretroviral therapy (ART) in HIV treatment?
What is the purpose of antiretroviral therapy (ART) in HIV treatment?
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Which phase of HIV infection is characterized by acute viral illness symptoms?
Which phase of HIV infection is characterized by acute viral illness symptoms?
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What complication is commonly associated with AIDS due to immune deficiency?
What complication is commonly associated with AIDS due to immune deficiency?
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What is a significant consequence of the loss of CD4+ T cells in HIV infection?
What is a significant consequence of the loss of CD4+ T cells in HIV infection?
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What is one of the goals of ongoing research related to HIV/AIDS?
What is one of the goals of ongoing research related to HIV/AIDS?
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In the chronic phase of HIV, what occurs regarding the host immune response?
In the chronic phase of HIV, what occurs regarding the host immune response?
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What is a primary mechanism behind the loss of CD4+ T cells during HIV infection?
What is a primary mechanism behind the loss of CD4+ T cells during HIV infection?
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What can signaling result in regarding transcription factors?
What can signaling result in regarding transcription factors?
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What is a primary characteristic of Mendelian disorders?
What is a primary characteristic of Mendelian disorders?
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Which type of mutation occurs when a DNA sequence is altered by the addition or deletion of nucleotides?
Which type of mutation occurs when a DNA sequence is altered by the addition or deletion of nucleotides?
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How can genetic abnormalities disrupt cellular homeostasis?
How can genetic abnormalities disrupt cellular homeostasis?
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What encompasses complex disorders?
What encompasses complex disorders?
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Which of the following disorders is caused by a mutation in the FBN1 gene?
Which of the following disorders is caused by a mutation in the FBN1 gene?
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In which type of genetic disorder are both copies of a gene mutated, affecting males and females equally?
In which type of genetic disorder are both copies of a gene mutated, affecting males and females equally?
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What role do alterations in non-coding RNAs, such as microRNAs, play?
What role do alterations in non-coding RNAs, such as microRNAs, play?
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Study Notes
Hemostasis and Thrombosis
- Coagulation is localized to sites of injury via mechanisms including activated platelets and endothelial phospholipid surfaces.
- Thrombomodulin, found on endothelial cells, converts thrombin into an anticoagulant.
- Fibrinolytic pathways regulate coagulation.
- Thrombosis is often related to endothelial injury, abnormal blood flow, or hypercoagulability.
- Thrombi can propagate, resolve, become organized, or embolize.
- Thrombosis induces tissue injury through vascular occlusion or embolization.
- Emboli are masses carried in blood to distant sites, frequently originating from dislodged thrombi.
- Pulmonary emboli primarily stem from lower-extremity deep vein thrombi and can lead to varied complications.
- Systemic emboli mainly arise from cardiac sources, and their consequences depend on the site of lodging.
- Fat embolism, amniotic fluid embolism, and air embolism are additional types of embolism with specific causes and manifestations.
- Infarcts are areas of ischemic necrosis caused by arterial or venous occlusion, presenting as hemorrhagic or pale appearances respectively.
Immune System
- Immunity safeguards against infections.
- The immune system comprises cells and molecules that protect the body from pathogens.
- Immune system defects can cause immunodeficiency diseases, rendering individuals susceptible to infections.
- The immune system can also cause tissue injury and hypersensitivity disorders.
- This chapter examines diseases caused by both insufficient and excessive immune responses.
- Amyloidosis is a disease characterized by the deposition of abnormal proteins in tissues.
- The immune response is composed of innate and adaptive immunity.
- Innate immunity is the immediate response to infections and is primarily associated with inflammation.
- Adaptive immunity is a specialized and potent response that neutralizes and eliminates pathogens.
- The innate immune system encompasses epithelial barriers, phagocytic cells, dendritic cells, natural killer cells, complement proteins, and pattern recognition receptors.
Innate Immunity
- The innate immune system identifies microbes and damaged cells through receptors such as Toll-like receptors.
Adaptive Immunity
- Lymphocytes are responsible for adaptive immunity and produce diverse receptors for antigens.
- T lymphocytes express T-cell receptors (TCRs) that recognize peptide fragments of antigens presented by MHC molecules.
Immune Deficiency Diseases
- Mutations in genes involved in lymphocyte maturation, function, or innate immunity can cause diseases such as:
- X-SCID
- Autosomal recessive SCID
- X-linked agammaglobulinemia (XLA)
- Di George syndrome
- X-linked hyper-IgM syndrome
- Common variable immunodeficiency
- Selective IgA deficiency
- X-SCID is characterized by the failure of T cell and B cell maturation due to a mutation in the common γ chain of a cytokine receptor.
- Autosomal recessive SCID results in the failure of T cell development and a secondary defect in antibody responses, frequently caused by a mutation in the gene encoding ADA.
- XLA is characterized by the failure of B cell maturation and the absence of antibodies due to mutations in the BTK gene.
- Di George syndrome is characterized by the failure of thymus development, leading to T cell deficiency.
- X-linked hyper-IgM syndrome leads to a failure to produce isotype-switched high-affinity antibodies due to mutations in genes encoding CD40L or activation-induced cytosine deaminase.
- Common variable immunodeficiency is characterized by defects in antibody production, with the cause unknown in most cases.
- Selective IgA deficiency results in a failure of IgA production, with an unknown cause.
- Deficiencies in innate immunity involve defects in leukocyte function, complement, and innate immune receptors.
- These immune deficiency diseases present with increased susceptibility to infections in early life.
Viral Infections
- Virus entry into cells requires CD4 and coreceptors, which are receptors for chemokines.
- Virus entry involves the binding of viral gp120 and fusion with the cell mediated by viral gp41 protein.
- The primary cellular targets for viral infection are CD4+ helper T cells, macrophages, and dendritic cells.
- Viral replication involves integration of the provirus genome into the host cell DNA and triggering of viral gene expression by stimuli that activate infected cells.
- The progression of infection involves acute infection of mucosal T cells and dendritic cells, viremia with dissemination of the virus, latent infection of cells in lymphoid tissue, and continuing viral replication and progressive loss of CD4+ T cells.
- Mechanisms of immune deficiency in viral infections include loss of CD4+ T cells through T cell death during viral replication and chronic stimulation-induced apoptosis, decreased thymic output, and functional defects.
- Defective macrophage and dendritic cell functions are also observed in viral infections.
- Destruction of the architecture of lymphoid tissues occurs in late stages of viral infections.
- Treatment of viral infections often involves antiviral drugs that target specific steps in the viral life cycle.
HIV Infection
- HIV is a viral infection that causes profound immune deficiency and AIDS.
- The HIV virus targets CD4+ T cells and progressively destroys them, weakening the immune system.
- The loss of CD4+ T cells in HIV infection is due to a combination of viral replication, chronic immune activation, and direct viral cytopathic effects.
- Immune deficiency caused by HIV infection increases the risk of opportunistic infections and certain types of cancer.
- Antiretroviral therapy (ART) is the standard treatment for HIV infection, suppressing viral replication and restoring immune function.
- ART involves the use of combinations of antiretroviral drugs that target different steps in the viral life cycle.
- Early initiation of ART and adherence to treatment are crucial for achieving viral suppression and preventing disease progression.
- Ongoing research aims to develop new strategies for the prevention, treatment, and cure of HIV/AIDS.
Stages of HIV Infection
- HIV infection advances through several phases: acute HIV infection, chronic (latent) phase, and AIDS.
- Acute HIV infection is characterized by manifestations of acute viral illness.
- During the chronic phase, the virus disseminates, the host immune response is activated, and there is progressive destruction of immune cells.
- AIDS refers to the severe immune deficiency that occurs in advanced stages of HIV infection.
- Full-blown AIDS manifests with various complications, mostly resulting from immune deficiency.
- Opportunistic infections are common in individuals with AIDS.
- Tumors, particularly those caused by oncogenic viruses, can occur in individuals with AIDS.
- Neurologic complications of unknown pathogenesis can occur in AIDS patients.
- Antiretroviral therapy (ART) has significantly reduced the incidence of opportunistic infections and tumors in individuals with HIV/AIDS.
- However, ART can also have numerous complications.
Amyloidosis
- Amyloidosis is a disorder characterized by the deposition of proteins that tend to aggregate and form insoluble fibrils.
Signaling Pathways
- Signaling can cause various effects, including enzyme activation or inactivation, nuclear or cytoplasmic localization of transcription factors, and actin polymerization or depolymerization.
- Transcription factors are activated or inactivated by signaling pathways, influencing gene expression.
- Feedback inhibitory or stimulatory loops can be activated as part of signaling pathways.
Genetics
- The completion of the Human Genome Project revealed that humans have approximately 25,000 protein-coding genes.
- Next-generation sequencing technologies enable rapid and cost-effective sequencing of the human exome, facilitating personalized medicine in the treatment of genetic diseases.
- Hereditary disorders are transmitted through generations, while congenital diseases are present at birth, but not all congenital diseases are genetic.
- Genetic abnormalities can affect protein structure and function, disrupting cellular homeostasis and contributing to disease.
- Mutations in protein-coding genes can result in point mutations, frameshift mutations, or trinucleotide repeat mutations.
- Structural variations, such as copy number changes or translocations, can also alter protein-coding genes and affect protein function.
- Alterations in non-coding RNAs, such as microRNAs and long non-coding RNAs, play important regulatory roles in gene expression.
- Genetic disorders can be categorized into Mendelian disorders, complex disorders, diseases arising from chromosomal abnormalities, and other genetic diseases with non-classic inheritance patterns.
- Mendelian disorders result from mutations in single genes and show high penetrance.
- Complex disorders involve multiple genes and environmental influences, while diseases arising from chromosomal abnormalities result from changes in chromosome number or structure.
Inheritance Patterns
- Autosomal dominant disorders affect males and females equally and can be transmitted by both sexes.
- Autosomal dominant disorders often involve dysfunctional receptors and structural proteins.
- Autosomal recessive diseases occur when both copies of a gene are mutated and frequently involve enzymes. Males and females are affected equally.
- X-linked disorders are transmitted by heterozygous females to their sons, while female carriers are usually unaffected due to random inactivation of one X chromosome.
Specific Genetic Disorders
- Marfan syndrome is caused by a mutation in the FBN1 gene, affecting connective tissues and activation of TGF-β.
- CAH is a group of autosomal recessive disorders characterized by defects in steroid biosynthesis. They are commonly caused by 21-hydroxylase deficiency.
- Reduction in cortisol production in CAH leads to compensatory ACTH secretion, resulting in androgen excess and virilization effects.
- Primary adrenocortical insufficiency can be acute (Waterhouse-Friderichsen syndrome) or chronic (Addison's disease).
- Chronic adrenal insufficiency is commonly caused by autoimmune adrenalitis in the context of autoimmune polyendocrine syndromes.
- Tuberculosis, opportunistic infections in HIV, and metastatic tumors are other important causes of chronic adrenal insufficiency.
- Common symptoms of adrenal insufficiency include fatigue, weakness, gastrointestinal disturbances, and high ACTH levels with associated skin pigmentation.
- Diabetes is characterized by the destruction of islet beta cells, while hypercortisolism is often caused by pituitary adenomas or adrenal neoplasms.
- Obesity is closely associated with insulin resistance and type 2 diabetes.
- Monogenic forms of diabetes are caused by single-gene defects affecting beta cell function or insulin signaling.
- Chronic adrenal insufficiency is often due to autoimmune adrenalitis or infections like tuberculosis.
- Symptoms of adrenal insufficiency include fatigue, weakness, gastrointestinal disturbances, and skin pigmentation.
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Test your understanding of hemostasis and thrombosis with this comprehensive quiz. Explore the mechanisms of coagulation, the role of thrombin, and the various types of emboli. Gain insights into the pathology related to thrombosis and its clinical implications.
